1. Field of the Invention
This invention relates to a chemical process for dealkylation of N-alkyl allylic tertiary amines as illustrated by the production of (+)-1-(p-methoxybenzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline from the corresponding N-methyl compound.
2. Description of the Prior Art
The analgesic generically (USAN) named butorphanol and chemically named (-)-17-(cyclobutylmethyl)-morphinan-3,14-diol has been described in U.S. Pat. No. 3,819,635 (and see also U.S. Pat. Nos. 3,775,414, 3,980,641 and 4,017,497).
An alternative synthesis of butorphanol starting with (+)-1-(p-methoxybenzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline has been disclosed by myself and my colleagues in U.S. application Ser. No. 669,795 filed Mar. 23, 1976. The pertinent disclosure therein is repeated at the end of this specification under the heading "Production of Butorphanol." 1-(p-Methoxybenzyl)-2-methyl-1,2,3,4,5,6,7,8-octahydroisoquinoline is believed to be commercially available and in any event its preparation has been described by Schnider et al., Helv. Chim. Acta, 33, 1437-1448 (1950) and its resolution into optical isomers by Schnider et al., Helv. Chim. Acta, 37, 710-720 (1954) [Chemical Abstracts, 45, 2010 (1951) and 49, 8975 (1955)].
A variety of reactions of amine oxides are reviewed in Mechanisms of Molecular Migrations edited by B. S. Thyagarajan, Volume 1, Interscience Publishers, N.Y., N.Y. 1968 in the section titled "The Polonovski Reaction" on pages 176-194.
Ferris et al., Detoxification Mechanisms. III. The Scope and Mechanism of the Iron-Catalyzed Dealkylation of Tertiary Amine Oxides, J. Org. Chem., 33(9), 3493-3498 (1968) report work as indicated by the title and also review earlier work such as that reported by Craig et al., Tertiary Amine Oxide Rearrangements. III. The Mechanism of the Demethylation of Nicotine, J. Amer. Chem. Soc., 86, 3866-3869(1964).
The Polonovski reaction has also been reviewed on pages 26-27 of Volume II of the Chemistry of Open-Chain Organic Nitrogen Compounds by Peter A. S. Smith, W. A. Benjamin, Inc., N.Y. (1966).